NM_017890.5:c.5334dupT
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_017890.5(VPS13B):c.5334dupT(p.Gly1779TrpfsTer5) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000992 in 1,613,078 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000089 ( 0 hom. )
Consequence
VPS13B
NM_017890.5 frameshift
NM_017890.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.114
Publications
0 publications found
Genes affected
VPS13B (HGNC:2183): (vacuolar protein sorting 13 homolog B) This gene encodes a potential transmembrane protein that may function in vesicle-mediated transport and sorting of proteins within the cell. This protein may play a role in the development and the function of the eye, hematological system, and central nervous system. Mutations in this gene have been associated with Cohen syndrome. Multiple splice variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]
VPS13B Gene-Disease associations (from GenCC):
- Cohen syndromeInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Myriad Women’s Health, Laboratory for Molecular Medicine, Orphanet, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 18 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 8-99641848-A-AT is Pathogenic according to our data. Variant chr8-99641848-A-AT is described in ClinVar as Pathogenic. ClinVar VariationId is 188881.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_017890.5. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| VPS13B | NM_017890.5 | MANE Plus Clinical | c.5334dupT | p.Gly1779TrpfsTer5 | frameshift | Exon 34 of 62 | NP_060360.3 | ||
| VPS13B | NM_152564.5 | MANE Select | c.5259dupT | p.Gly1754TrpfsTer5 | frameshift | Exon 34 of 62 | NP_689777.3 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| VPS13B | ENST00000358544.7 | TSL:1 MANE Plus Clinical | c.5334dupT | p.Gly1779TrpfsTer5 | frameshift | Exon 34 of 62 | ENSP00000351346.2 | Q7Z7G8-1 | |
| VPS13B | ENST00000357162.7 | TSL:1 MANE Select | c.5259dupT | p.Gly1754TrpfsTer5 | frameshift | Exon 34 of 62 | ENSP00000349685.2 | Q7Z7G8-2 | |
| VPS13B | ENST00000521559.1 | TSL:3 | c.420dupT | p.Gly141fs | frameshift | Exon 4 of 4 | ENSP00000428809.1 | H0YB72 |
Frequencies
GnomAD3 genomes 0.0000197 AC: 3AN: 152170Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
3
AN:
152170
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
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Gnomad AMR
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Gnomad ASJ
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Gnomad FIN
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Gnomad NFE
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Gnomad OTH
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GnomAD4 exome AF: 0.00000890 AC: 13AN: 1460908Hom.: 0 Cov.: 31 AF XY: 0.00000826 AC XY: 6AN XY: 726596 show subpopulations
GnomAD4 exome
AF:
AC:
13
AN:
1460908
Hom.:
Cov.:
31
AF XY:
AC XY:
6
AN XY:
726596
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33452
American (AMR)
AF:
AC:
0
AN:
44580
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26110
East Asian (EAS)
AF:
AC:
0
AN:
39674
South Asian (SAS)
AF:
AC:
0
AN:
86144
European-Finnish (FIN)
AF:
AC:
0
AN:
53386
Middle Eastern (MID)
AF:
AC:
0
AN:
5762
European-Non Finnish (NFE)
AF:
AC:
13
AN:
1111446
Other (OTH)
AF:
AC:
0
AN:
60354
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.498
Heterozygous variant carriers
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome 0.0000197 AC: 3AN: 152170Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74336 show subpopulations
GnomAD4 genome
AF:
AC:
3
AN:
152170
Hom.:
Cov.:
32
AF XY:
AC XY:
2
AN XY:
74336
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41450
American (AMR)
AF:
AC:
0
AN:
15278
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5192
South Asian (SAS)
AF:
AC:
0
AN:
4822
European-Finnish (FIN)
AF:
AC:
0
AN:
10610
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
3
AN:
68024
Other (OTH)
AF:
AC:
0
AN:
2094
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.508
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Variant carriers
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Age
Alfa
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Bravo
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ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
3
-
-
Cohen syndrome (3)
1
-
-
not provided (1)
1
-
-
VPS13B-related disorder (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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